The purpose of the study is to find out which is a better treatment for diabetic macular edema (DME): laser alone, laser combined with an intravitreal injection of triamcinolone, laser combined with an intravitreal injection of ranibizumab, or intravitreal injection of ranibizumab alone. At the present time, it is not known whether intravitreal steroid or anti-vascular endothelial growth factor (anti-VEGF) injections, with or without laser treatment, are better than just laser by itself. It is possible that one or both of the types of injections, with or without laser treatment, will improve vision more often than will laser without injections. However, even if better vision outcomes are seen with injections, side effects may be more of a problem with the injections than with laser. Therefore, this study is conducted to find out whether the benefits of the injections will outweigh the risks.

Further study details as provided by Diabetic Retinopathy Clinical Research Network:

Primary Outcome Measures:

Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method.

Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

Secondary Outcome Measures:

Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: No ]

Negative change denotes an improvement.

Number of Injections in First Year [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: No ]

Number of Laser Treatments Received Prior to the 1 Year Visit [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

One eye in the sham+prompt laser group did not receive laser until post 1-year due to an adverse event unrelated to study treatment. One eye in the triamcinolone+prompt laser did not receive laser until after 1-year due to missing 2 consecutive visits at the time of required laser treatment.

Logarithmic transformation of optical coherence tomography central subfield thickness is calculated by taking the log base 10 of the ratio of the central subfield thickness divided by 200 and rounding to the nearest hundredth. The change is the change in the log values.

Eyes With Alternative Treatments Prior to the 1-year Visit [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

Each combination of treatment only counted once.

Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

113 eyes had missing or ungradable photos at 1 year. Criteria are based on the ETDRS fundus photographic risk factors for the progression of diabetic retinopathy. ETDRS report no. 12. Ophthalmology 1991; 98:823-833

Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

Antiplatelet Trialists' Collaboration is a collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. MBJ 1994; 308:81-106. Nonfatal cerebrovascular accident includes ischemic or hemorrhagic or unknown events. Vascular death includes death from any potential vascular or unknown cause.

Major Ocular Adverse Events During First Year of Follow-Up [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.

For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.

Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first 12 months of the study.

Study Eye Inclusion Criteria

The subject must have one eye meeting all of the inclusion criteria and none of the exclusion criteria listed below. A subject may have two study eyes only if both are eligible at the time of randomization.

If prior macular photocoagulation has been performed, the investigator believes that the study eye may possibly benefit from additional photocoagulation.

Study Eye Exclusion Criteria

The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye):

Macular edema is considered to be due to a cause other than diabetic macular edema.

An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition).

An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)

Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).

History of treatment for diabetic macular edema at any time in the past 4 months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-VEGF drugs, or any other treatment).

History of panretinal (scatter) photocoagulation (PRP) within 4 months prior to randomization.

Anticipated need for PRP in the 6 months following randomization.

History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization.

History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to randomization.

Aphakia.

Intraocular pressure >= 25 mmHg.

History of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma; note: history of angle-closure glaucoma is not an exclusion criterion).

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00444600